Continuous delivery of rotigotine decreases extracellular dopamine suggesting continuous receptor stimulation Short communication First Online: 16 April 2007 Received: 20 December 2006 Accepted: 07 March 2007 DOI:
Cite this article as: Kehr, J., Hu, XJ., Goiny, M. et al. J Neural Transm (2007) 114: 1027. doi:10.1007/s00702-007-0719-3 Summary
Rotigotine, a non-ergolinic dopamine receptor agonist for treatment of Parkinson’s disease was continuously administered over 48 h (0.5 mg/kg s.c., slow release formulation) to conscious rats striatally implanted with a microdialysis probe. Subsequently, the levels of rotigotine increased to a maximum of 3.42 + 2.1 nmol/l and remained at a level of 2.81 ± 0.82 nmol/l for 48 h. Concomitantly, the dopamine levels consistently decreased to 20% of the control level. This suggests that the sustained administration of rotigotine provides stable extracellular drug levels in the striatum resulting in continuous stimulation of dopamine receptors.
Keywords: Parkinson’s disease, treatment, dyskinesia, rat, microdialysis, extracellular drug concentration, pharmacokinetics References Aretha, CW, Sinha, A, Galloway, MP 1995 Dopamine D3-preferring ligands act at synthesis modulating autoreceptors J Pharmacol Exp Ther 274 609 613 PubMed Google Scholar Bibbiani, F, Costantini, LC, Patel, R, Chase, TN 2005 Continuous dopaminergic stimulation reduces risk of motor complications in parkinsonian primates Exp Neurol 192 73 78 CrossRef PubMed Google Scholar de Boer, P, Enrico, P, Wright, J, Wise, LD, Timmerman, W, Moor, E, et al. 1997 Characterization of the effect of dopamine D3 receptor stimulation on locomotion and striatal dopamine levels Brain Res 758 83 91 CrossRef PubMed Google Scholar de Lange, EC, Bouw, MR, Mandema, JW, Danhof, M, de Boer, AG, Breimer, DD 1995 Application of intracerebral microdialysis to study regional distribution kinetics of drugs in rat brain Br J Pharmacol 116 2538 2544 PubMed Google Scholar de Lange, EC, de Boer, AG, Breimer, DD 2000 Methodological issues in microdialysis sampling for pharmacokinetic studies Adv Drug Deliv Rev 45 125 148 CrossRef PubMed Google Scholar Elmquist, WF, Sawchuk, RJ 1997 Application of microdialysis in pharmacokinetic studies Pharm Res 14 267 288 CrossRef PubMed Google Scholar Elmquist, WF, Sawchuk, RJ 2000 Use of microdialysis in drug delivery studies Adv Drug Deliv Rev 45 123 124 CrossRef PubMed Google Scholar Guldenpfennig, WM, Poole, KH, Sommerville, KW, Boroojerdi, B 2005 Safety, tolerability, and efficacy of continuous transdermal dopaminergic stimulation with rotigotine patch in early-stage idiopathic Parkinson disease Clin Neuropharmacol 28 106 110 CrossRef PubMed Google Scholar Hammarlund-Udenaes, M, Paalzow, LK, de Lange, EC 1997 Drug equilibration across the blood–brain barrier — pharmacokinetic considerations based on the microdialysis method Pharm Res 14 128 134 CrossRef PubMed Google Scholar Jenner, P 2005 A novel dopamine agonist for the transdermal treatment of Parkinson’s disease Neurology 65 S3 S5 CrossRef PubMed Google Scholar Kehr, J 1999 Monitoring chemistry of brain microenvironment: biosensors, microdialysis and related techniques Windhorst, U Johansson, H eds. Modern techniques in neuroscience research Springer Berlin Heidelberg New York, Tokyo 1149 1198 Google Scholar Kehr, J, Hu, X-J, Yoshitake, T, Scheller, D 2006 Determination of the dopamine agonist rotigotine in microdialysates from the rat brain by microbore column liquid chromatography with electrochemical detection J Chromatography B Analyt Technol Biomed Life Sci 845 109 113 CrossRef Google Scholar Le Quellec, A, Dupin, S, Genissel, P, Saivin, S, Marchand, B, Houin, G 1995 Microdialysis probes calibration: gradient and tissue dependent changes in no net flux and reverse dialysis methods J Pharmacol Toxicol Methods 33 11 16 CrossRef PubMed Google Scholar LeWitt, P 2005 Rotigotine: a viewpoint by Peter LeWitt CNS Drugs 19 983 984 CrossRef PubMed Google Scholar O’Hara, CM, Uhland-Smith, A, O’Malley, KL, Todd, RD 1996 Inhibition of dopamine synthesis by dopamine D2 and D3 but not D4 receptors J Pharmacol Exp Ther 277 186 192 PubMed Google Scholar Parkinson Study Group 2003 A controlled trial of rotigotine monotherapy in early Parkinson’s disease Arch Neurol 60 1721 1728 CrossRef Google Scholar Poewe, W, Luessi, F 2005 Clinical studies with transdermal rotigotine in early Parkinson’s disease Neurology 65 S11 S14 PubMed Google Scholar Reynolds, NA, Wellington, K, Easthope, SE 2005 Rotigotine: in Parkinson’s disease CNS Drugs 19 973 981 CrossRef PubMed Google Scholar Roth, RH, Nowycky, MC 1977 Nonstriatal dopaminergic neurons: role of presynaptic receptors in the modulation of transmitter synthesis Adv Biochem Psychopharmacol 16 465 470 PubMed Google Scholar Scheller, DKA 2006 Extended receptor profile of rotigotine, a non-ergolinic dopamine agonist being investigated in Parkinson’s disease Mov Disord 21 S80 Google Scholar Scheller, D, Kolb, J 1991 The internal reference technique in microdialysis: a practical approach to monitoring dialysis efficiency and to calculating tissue concentration from dialysate samples J Neurosci Methods 40 31 38 CrossRef PubMed Google Scholar Timmerman, W, Westerink, BH, De Vries, JB, Tepper, PG, Horn, AS 1989 Microdialysis and striatal dopamine release: stereoselective actions of the enantiomers of N-0437 Eur J Pharmacol 162 143 150 CrossRef PubMed Google Scholar Ungerstedt, U 1991 Microdialysis — principles and applications for studies in animals and man J Intern Med 230 365 373 CrossRef PubMed Google Scholar Wang, X, Patsalos, PN 2003 A comparison of central brain (cerebrospinal and extracellular fluids) and peripheral blood kinetics of phenytoin after intravenous phenytoin and fosphenytoin Seizure 12 330 336 CrossRef PubMed Google Scholar Westfall, TC, Besson, MJ, Giorguieff, MF, Glowinski, J 1976 The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum Naunyn Schmiedebergs Arch Pharmacol 292 279 287 CrossRef PubMed Google Scholar